Cigarette smoking is the single most preventable cause of morbidity and mortality in the United States, accounting for approximately 427,000 deaths each year [(2000) Morbidity and Mortality Weekly Report 49:1–27]. Nicotine is widely accepted as the tobacco substance that causes addiction [Benowitz (1991) Br. J Addict. 86:495–499; Henningfield et al. (1983) Pharmacol. Biochem. Behav. 19:887–890; and Stolerman and Jarvis (1995) Psychopharmacol. 117:2–10]. Current pharmacotherapies available for those attempting to quit smoking generally involve nicotine replacement and bupropion, which approximately doubles the cessation rate versus placebo [Hughes et al. (1999) Nicotine Tob. Res. 1: 169–174]. However, even with concomitant behavioral therapy, long-term success rates range from 25 to 45 percent [Fiore et al. (2000) WMJ 99:68–72]. New therapies are needed, particularly for those with psychiatric co-morbidity and for anyone failing existing therapies [Hughes et al. supra; Rennard and Daughton (2000) Chest 117:360S-364S].